RRC ID 46532
著者 Wu X, Shi Z, Cui M, Han M, Ruvkun G.
タイトル Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway chromatin complexes.
ジャーナル PLoS Genet
Abstract The retinoblastoma (Rb) tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene.
巻・号 8(3)
ページ e1002542
公開日 2012-1-1
DOI 10.1371/journal.pgen.1002542
PII PGENETICS-D-11-01180
PMID 22412383
PMC PMC3297578
MeSH Animals Argonaute Proteins / genetics Argonaute Proteins / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cell Lineage* / genetics Cell Proliferation Chromatin* / genetics Chromatin* / metabolism Gene Expression Regulation, Developmental Germ Cells* / metabolism Mutation RNA Interference* Repressor Proteins* / genetics Repressor Proteins* / metabolism SUMO-1 Protein / genetics SUMO-1 Protein / metabolism
IF 5.175
引用数 32
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm2649 tm1637 tm894 tm1200